The female ovulation, or menstrual, cycle occurs every 28 to 30 days on average, measured from the onset of menstruation. Three significant events can occur in conjunction with the menstrual cycle: ovulation, pregnancy, and menopause. Ovulation marks the beginning of a period of fertility while pregnancy follows from the fertilization of an ovum. Menopause marks the final menstrual event. Determining and monitoring ovulation, pregnancy and menopause is important.
Conception in a human female can only occur during periods of fertility, typically in the 24 through 36 hours following ovulation. For couples desiring conception, accurately determining the time of ovulation is critical. Conversely, certain religious, ethnic and social groups prohibit the use of active forms of contraception and rely on abstinence during periods of female fertility as the sole means of birth control. At around age 50, most women begin to experience a number of endocrinal changes as menopause approaches due to a loss of ovarian follicular activity. A period of hormonal changes can last up to four years, during which time many women experience adverse symptoms, including hot flashes, night sweats, sleeplessness, vaginal dryness and mood swings. Hormone replacement therapy, providing estrogen and progestin in combination, or estrogen replacement therapy, providing estrogen alone, can be prescribed to treat and counter potential undesired side effects arising from menopause or premature ovarian failure. Hormone replacement therapy will be used herein to refer to both therapies involving combined estrogen and progestin treatment as well as estrogen treatment alone.
Presently, up to 20% of menopausal women use some form of hormone replacement therapy in the United States. Recent studies on hormone replacement therapy suggest an increase in the risk for cancer and heart disease and recommend that the levels of hormones dosed be closely monitored and adjusted on an individual basis. Safely providing appropriate hormone replacement therapy requires an accurate historical record of menstrual cycle-related hormonal levels to provide an accurate basis for initial and ongoing dosing levels.
The menstrual cycle begins at menarche and ends at menopause, and proceeds in four stages. The first stage, menstruation, lasts four to five days and is characterized by the shedding of the endometrial lining of the uterus and menstrual discharge. The second stage, pre-ovulation, or the estrogenic phase, lasts from 10 to 16 days, during which time a follicle (egg sac) containing an ovum forms inside one of the ovaries. The third stage, ovulation, lasts from 24 to 36 hours, occurring about Day 14 in a 28-day cycle, and takes place when the follicle ruptures, releasing a mature ovum into a Fallopian tube and thence into the uterus. The last stage, the luteal or progestational phase, takes about 11 to 14 days following ovulation, during which time the ruptured follicle, or corpus luteum, withers and is reabsorbed by the body if fertilization has not occurred. If pregnancy occurred, the level of human chorionic gonadotrophin (hCG) increases six to ten days following ovulation.
The menstrual cycle is controlled primarily by an interplay of four hormones: estrogen, progesterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH). About mid-cycle, just prior to ovulation, the level of estrogen rises, triggering a surge in LH, accompanied by a transient rise in basal body temperature. These events signal that ovulation is imminent. Thus, LH level and basal body temperature are most often monitored to determine fertility.
Similarly, the onset of menopause is characterized by significant endocrinal changes, including a decrease in the production of estrogen, progesterone and testosterone, followed by a measurable increase in FSH at the cessation of ovarian follicular activity. Generally, a woman has reached menopause when FSH blood level rises above 30 to 40 MIU/ml. Estrogen, as estradiol or estrone, is also sometimes measured in determining whether menopause has occurred.
Reliance on a single factor, particularly a specific hormone, is misplaced. Hormone levels, and therefore the menstrual cycle, and menopause, can be affected heavily by external and physiological factors and can be erratic and difficult to predict. These factors include physiological stress, health and well-being, drugs, ovarian cysts, sexually transmitted diseases, and others. Thus, the menstrual cycle and menopause are best monitored by observing the interplay of all four hormones, rather than just LH or basal body temperature.
Measuring multiple hormones, though, is time-consuming and difficult in a non-clinical environment. Individual tests are required to detect the level of each hormone and the presence of each will depend on the point in the menstrual cycle at which measurement occurs. In addition, a single battery of hormone tests represents at best a snapshot of hormonal levels and is meaningless without applying a historical perspective of previous hormone levels over the present and past menstrual cycles.
In the prior art, historical menstrual cycle data has been used for determining and monitoring reproductive physiological stages based on a lay understanding of ovulation. The calendar or rhythm method of family planning relies on pinpointing the time of ovulation based on past menstrual cycles to increase the chances of, or to avoid, conception. Due to the variance inherent in menstrual cycles, though, the calendar method is marginal at best and often unreliable.
Similarly, the basal body temperature method attempts to identify the time of ovulation based on the transient body temperature increase which generally precedes ovulation, such as described in U.S. Pat. No. 5,657,762 to Coley et al, issued Aug. 19, 1997, the disclosure of which is incorporated by reference. However, basal body temperature can be skewed by other, non-ovulation related events, rendering basal body temperature measurements an unreliable indicator. As well, the shift in body temperature can be out of synchrony with ovulation by as much as three to six days instead of the expected 24 to 36 hours.
Ferning tests are also used to detect the period of ovulation, such as described in U.S. Pat. No. 6,159,159 to Canter et al, issued Dec. 12, 2000, the disclosure of which is incorporated by reference. Ferning occurs in dried saliva observed four to six days prior to ovulation and is roughly correlated to increases in chloride content. Determining the presence of ferning requires a low-magnification lens and is qualitative. The basis of the ferning test has not been scientifically proven and the subjectivity of the ferning test undermines the reliability of determining ovulation using this method.
Analogously, the onset of menopause can be tested at home using a blood test that measures circulating FSH levels. Menopause onset can also be tested based on FSH levels in the urine, typically read at a level of 25 IU/L, which corresponds directly with blood serum levels. However, FSH level alone can only serve at best as a general guide to the onset of menopause.
Presently, numerous devices are available commercially for testing hormone levels in a non-clinical environment, particularly at home. These devices typically perform an assay of a readily-obtainable sample of biological material, such as urine, blood or saliva, and provide a result probative of a relative hormone level. However, at best, each test results in a qualitative indicator based a subjective reading. Single result outcomes, such as provided by such at-home tests, provide limited information. Moreover, aberrations between single reading tests are common and multiple tests must be performed to obtain a more comprehensive picture of overall hormonal levels.
For example, U.S. Pat. No. 5,602,040 to May et al., issued Feb. 11, 1997, the disclosure of which is incorporated by reference, describes an analytical test device useful in pregnancy testing. A dry porous carrier protrudes from an enclosing hollow casing to receive a liquid biological sample. A labeled specific binding reagent becomes freely mobile within the porous carrier when moistened and a liquid sample permeates into a second zone comprising an unlabeled specific binding reagent for the same analyte, thereby enabling the extent to which the labeled reagent becomes bound in the second zone to be observed. In addition, a device arranging multiple discrete bodies of porous solid phase material in parallel to obtain multiple analytical results from a single sample simultaneously is described. However, the May device fails to disclose providing unidirectional liquid flow channels facilitating uniform sample distribution and deposition.
Therefore, there is a need for an approach to monitoring multiple hormones on a preferably regular basis throughout the menstrual cycle to determine fertility through ovulation, pregnancy and the onset of menopause. Preferably, such an approach would be easily used in a non-clinical environment and avoid a reliance on test results from a single hormone.
There is a further need for an approach to maintaining a historical data bank of hormone levels throughout one or more menstrual cycles. Preferably, such an approach would provide an accurate weighing of the various factors relating to a menstrual cycle and for use in determining and monitoring reproductive physiological stages, in medical diagnoses, and in hormone or estrogen replacement therapy during menopause.
Therefore, there is a need for a testing approach for providing accurate readings of a plurality of hormones obtained from a single liquid biological sample, preferably configurable as a lay test for use in a non-clinical at-home environment. Preferably, such an approach would facilitate historical tracking of multiple hormone levels recorded over one or more menstrual cycles.